1. Issue: The results of metabolism studies submitted to the Agency and
of metabolism and mechanistic studies reported in the literature show that carbon
disulfide is a common neuropathic metabolite formed by the dithiocarbamates.

Question: Please comment on the evidence supporting the conclusion that
carbon disulfide is a common metabolic product of the dithiocarbamates and that
carbon disulfide is a neuropathic moiety. Lead Discussants: Jeanne Harry, Ph.D., Michael McClain, Ph.D. and John O'Donoghue,
Ph.D.

2. Issue: Distal peripheral neuropathy was identified as the most
common, sensitive effect for grouping the dithiocarbamates based on the potential
to induce a common effect.

Question: Please comment on the evidence supporting the selection of
distal peripheral neuropathy as the endpoint of choice for grouping the dithiocarbamates
based on the potential to induce a common effect.Lead Discussants: David Dorman, Ph.D. and Ernest McConnell, DVM

3. Issue: Although Na-dimethyldithiocarbamate and ferbam are presumed
to form carbon disulfide during metabolism, results of studies with these pesticides
have not shown neuropathic effects.

Question: Please comment on the recommendation that Na-dimethyldithiocarbamate
and ferbam be excluded from the common mechanism group of neuropathic dithiocarbamates.
Lead Discussants: Diane Miller, Ph.D. and John O'Donoghue, Ph.D.

3:30 PM BREAK

3:45 PM Panel Discussion (continued)

II. Thiocarbamates

1. Issue: Although there are data available from the literature and from
results of studies submitted to OPP that indicate the thiocarbamate pesticides
share a common metabolic profile, there appears to be a lack of information on
the specific mechanism of action that can account for the neuropathology that
is induced in rats following treatment with a thiocarbamate. Unlike the dithiocarbamates,
the thiocarbamates do not undergo conversion to the common metabolite, carbon
disulfide.

Question: Please comment on the evidence that supports a presumption that
the thiocarbamates may have a common mechanism of toxicity but a common mechanism
of toxicity has not been linked to a critical metabolic moiety. Lead Discussants: John O'Donoghue, Ph.D. and Kendall Wallace, Ph.D.

2. Issue: Treatment of rats with a thiocarbamate may result in the formation
of neuropathological lesions, developmental/reproductive toxicity, or decrease
cholinesterase activity. The current assessment identified distal peripheral neuropathy
as the most sensitive, common effect of the thiocarbamates.

Question: Would the panel please comment on the selection of the neuropathological
endpoint as the appropriate endpoint for grouping the thiocarbamate pesticides
based on the potential to induce a common effect.Lead Discussants: Ernest McConnell, DVM and David Dorman, Ph.D.

3. Issue: The document Thiocarbamates: A Screening Level Cumulative
Dietary (Food) Risk Assessment presents a step-wise screening process for
conducting a cumulative risk assessment. This screening level approach is intended
to identify whether there is a need to initiate a more comprehensive cumulative
risk assessment for a small group of structurally related pesticides that induce
a common effect. It is not intended to identify a level of concern or risk for
any one chemical or a group of chemicals that share a common mechanism of toxicity.

Please be advised that agenda times are approximate. For further information,
please contact the Designated Federal Official for this meeting, Mr. Paul Lewis,
via telephone: (703) 305-5369; fax: (703) 605-0656; or email:lewis.paul@epa.gov.